5cfa | pdb_00005cfa
Crystal structures of Bbp from Staphylococcus aureus with peptide ligand
Structural highlights
Disease[FIBA_HUMAN] Defects in FGA are a cause of congenital afibrinogenemia (CAFBN) [MIM:202400]. This is a rare autosomal recessive disorder characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Note=The majority of cases of afibrinogenemia are due to truncating mutations. Variations in position Arg-35 (the site of cleavage of fibrinopeptide a by thrombin) leads to alpha-dysfibrinogenemias. Defects in FGA are a cause of amyloidosis type 8 (AMYL8) [MIM:105200]; also known as systemic non-neuropathic amyloidosis or Ostertag-type amyloidosis. AMYL8 is a hereditary generalized amyloidosis due to deposition of apolipoprotein A1, fibrinogen and lysozyme amyloids. Viscera are particularly affected. There is no involvement of the nervous system. Clinical features include renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash.[1] Function[BBP_STAAU] Specifically interacts with bone sialoprotein (BSP), a glycoprotein of bone and dentin extracellular matrix. Could contribute to staphylococcal osteomyelitis and arthritis.[2] [FIBA_HUMAN] Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation. Publication Abstract from PubMedBone sialoprotein-binding protein (Bbp), a MSCRAMMs (Microbial Surface Components Recognizing Adhesive Matrix Molecules) family protein expressed on the surface of Staphylococcus aureus (S. aureus), mediates adherence to fibrinogen alpha (Fg alpha), a component in the extracellular matrix of the host cell and is important for infection and pathogenesis. In this study, we solved the crystal structures of apo-Bbp(273-598) and Bbp(273-598)-Fg alpha(561-575) complex at a resolution of 2.03 A and 1.45 A, respectively. Apo-Bbp(273-598) contained the ligand binding region N2 and N3 domains, both of which followed a DE variant IgG fold characterized by an additional D1 strand in N2 domain and D1' and D2' strands in N3 domain. The peptide mapped to the Fg alpha(561-575) bond to Bbp(273-598) on the open groove between the N2 and N3 domains. Strikingly, the disordered C-terminus in the apo-form reorganized into a highly-ordered loop and a beta-strand G covering the ligand upon ligand binding. Bbp(Ala298-Gly301) in the N2 domain of the Bbp(273-598)-Fg alpha(561-575) complex, which is a loop in the apo-form, formed a short alpha-helix to interact tightly with the peptide. In addition, Bbp(Ser547-Gln561) in the N3 domain moved toward the binding groove to make contact directly with the peptide, while Bbp(Asp338-Gly355) and Bbp(Thr365-Tyr387) in N2 domain shifted their configurations to stabilize the reorganized C-terminus mainly through strong hydrogen bonds. Altogether, our results revealed the molecular basis for Bbp-ligand interaction and advanced our understanding of S. aureus infection process. Crystal structures of Bbp from Staphylococcus aureus reveal the ligand binding mechanism with Fibrinogen alpha.,Zhang X, Wu M, Zhuo W, Gu J, Zhang S, Ge J, Yang M Protein Cell. 2015 Oct;6(10):757-66. doi: 10.1007/s13238-015-0205-x. Epub 2015, Sep 8. PMID:26349459[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
